C–H Activation: Toward Sustainability and Applications

[Image: see text] Since the definition of the “12 Principles of Green Chemistry” more than 20 years ago, chemists have become increasingly mindful of the need to conserve natural resources and protect the environment through the judicious choice of synthetic routes and materials. The direct activation and functionalization of C–H bonds, bypassing intermediate functional group installation is, in abstracto, step and atom economic, but numerous factors still hinder the sustainability of large-scale applications. In this Outlook, we highlight the research areas seeking to overcome the sustainability challenges of C–H activation: the pursuit of abundant metal catalysts, the avoidance of static directing groups, the replacement of metal oxidants, and the introduction of bioderived solvents. We close by examining the progress made in the subfield of aryl C–H borylation from its origins, through highly efficient but precious Ir-based systems, to emerging 3d metal catalysts. The future growth of this field will depend on industrial uptake, and thus we urge researchers to strive toward sustainable C–H activation.